During 1940-1980s, heavy uranium (U) mining took place on the Navajo Reservation. Navajo miners were not informed of health risks associated with U mining, thus did not take precautions to protect themselves or their families. More than 1000 mines were not properly closed, potentially leading to continued exposure. Many Navajos suffer from maladies thought to be from U exposure. Most notable is a 17 times greater incidence of gonadal, germ cell, and genital cancer in Navajo girls who lived near U mining. Many heavy metals are estrogenic; however, U has not been examined. Preliminary data demonstrate U stimulation of MCF-7 breast cancer cell proliferation and an increase in uterine weight in U treated ovariectomized mice. The hypothesis that U mimics 17-estradiol in vitro to elicit estrogen-sensitive responses will be tested. In vitro estrogenicity of uranium will be examined in an estrogen receptor binding assay and MCF-7 cell proliferation. Additionally, U and ER interaction will be visualized by EM and confocal microscopy.